2017 Epid Sesi 13 MH STROBE
Strengthening the Reporting of
Observational studies in Epidemiology
(STROBE)
Table 1.
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007) Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE): Explanation and Elaboration. PLOS Medicine 4(10): e297. https://doi.org/10.1371/journal.pmed.0040297
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0040297
TITLE and ABSTRACT
1.
(a I di ate the stud s desig ith a o
used term in the title or the abstract
Example
o l
Leukaemia incidence among workers in the shoe
and boot manufacturing industry: a case-control
stud
TITLE and ABSTRACT
1.
(b) Provide in the abstract an informative and
balanced summary of what was done and what
was found
TITLE and ABSTRACT
Example
Background: The expected survival of HIV-infected
patients is of major public health interest.
Objective: To estimate survival time and age-specific
mortality rates of an HIV-infected population
compared with that of the general population.
Design: Population-based cohort study.
Setting: All HIV-infected persons receiving care in
Denmark from 1995 to 2005.
TITLE and ABSTRACT
Example
Patients: Each member of the nationwide Danish HIV
Cohort Study was matched with as many as 99 persons
from the general population according to sex, date of
birth, and municipality of residence.
Measurements: The authors computed Kaplan–Meier
life tables with age as the time scale to estimate survival
from age 25 years. Patients with HIV infection and
corresponding persons from the general population
ere o ser ed fro the date of the patie t s HIV
diagnosis until death, emigration, or 1 May 2005.
TITLE and ABSTRACT
Example
Results: 3990 HIV-infected patients and 379 872 persons from the
general population were included in the study, yielding 22 744
(median, 5.8 y/person) and 2 689 287 (median, 8.4 years/person)
person-years of observation. Three percent of participants were
lost to follow-up. From age 25 years, the median survival was 19.9
years (95% CI, 18.5 to 21.3) among patients with HIV infection and
51.1 years (CI, 50.9 to 51.5) among the general population. For HIVinfected patients, survival increased to 32.5 years (CI, 29.4 to 34.7)
during the 2000 to 2005 period. In the subgroup that excluded
persons with known hepatitis C coinfection (16%), median survival
was 38.9 years (CI, 35.4 to 40.1) during this same period. The
relative mortality rates for patients with HIV infection compared
with those for the general population decreased with increasing
age, whereas the excess mortality rate increased with increasing
age.
TITLE and ABSTRACT
Example
Limitations: The observed mortality rates are
assumed to apply beyond the current maximum
observation time of 10 years.
Conclusions: The estimated median survival is more
than 35 years for a young person diagnosed with HIV
infection in the late highly active antiretroviral
therapy era. However, an ongoing effort is still
needed to further reduce mortality rates for these
persons compared with the general population.
INTRODUCTION
2. Background/rationale
Explain the scientific background and rationale for the
investigation being reported
INTRODUCTION
Example
Co er s a out the risi g pre ale e of o esit i hildre a d
adolescents have focused on the well documented associations between
childhood obesity and in- creased cardiovascular risk and mortality in
adulthood. Childhood obesity has considerable social and psychological
consequences within childhood and adolescence, yet little is known about
social, socioeconomic, and psychological con- sequences in adult life. A
recent systematic review found no longitudinal studies on the outcomes
of childhood obesity other than physical health outcomes and only two
longitudinal studies of the socioeconomic effects of obesity in
adolescence. Gortmaker et al. found that US women who had been obese
in late adolescence in 1981 were less likely to be married and had lower
incomes seven years later than women who had not been overweight,
while men who had been overweight were less likely to be married.
Sargent et al. found that UK women, but not men, who had been obese at
16 years in 1974 earned 7.4% less than their non-obese peers at age 23. (.
. .) We used longitudinal data from the 1970 British birth cohort to
examine the adult socioeconomic, educational, social, and psychological
out o es of hildhood o esit
INTRODUCTION
3. Objectives
State specific objectives, including any prespecified
hypotheses
INTRODUCTION
Example
Our pri ar o je ti es ere to deter i e the
prevalence of domestic violence among female
patients presenting to four community-based,
primary care, adult medicine practices that serve
patients of diverse socio- economic background and
2) identify demographic and clinical differences
between currently abused patients and patients not
currently being abused.
METHODS
4. Study design
Present key elements of study design early in the paper
METHODS
Example
We used a ase-crossover design, a variation of a case- control
desig that is appropriate he a rief e posure dri er s pho e
use) causes a transient rise in the risk of a rare outcome (a crash).
We o pared a dri er s use of a o ile pho e at the esti ated
ti e of a rash ith the sa e dri er s use duri g a other suita le
time period. Because drivers are their own controls, the design
controls for characteristics of the driver that may affect the risk of a
crash but do not change over a short period of time. As it is
important that risks during control periods and crash trips are
similar, we compared phone activity during the hazard interval
(time immediately before the crash) with phone activity during
control intervals (equivalent times during which participants were
driving but did not crash) in the previous eek.
METHODS
5. Setting
Describe the setting, locations, and relevant dates,
including periods of recruitment, exposure, follow-up, and
data collection
METHODS
Example
The Pasitos Cohort Study recruited pregnant women
from Women, Infant and Child clinics in Socorro and San
Elizario, El Paso County, Texas and maternal-child clinics
of the Mexican Social Security Institute in Ciudad Juarez,
Mexico from April 1998 to October 2000. At baseline,
prior to the birth of the enrolled cohort children, staff
interviewed mothers regarding the household
environment. In this ongoing cohort study, we target
follow-up exams at 6-month intervals beginning at age 6
o ths.
METHODS
6. Participants
(a). Cohort study—Give the eligibility criteria, and the
sources and methods of selection of participants. Describe
methods of follow-up
METHODS
Example
Parti ipa ts i the Io a Wo e s Health Stud ere a
random sample of all women ages 55 to 69 years derived
fro the state of Io a auto o ile dri er s li e se list i
,
which represented approximately 94% of Iowa women in that
age group. (. . .) Follow-up questionnaires were mailed in
October 1987 and August 1989 to assess vital status and
address changes. (. . .) Incident cancers, except for nonmelanoma skin cancers, were ascertained by the State Health
‘egistr of Io a . . . . The Io a Wo e s Health Stud ohort
was matched to the registry with combinations of first, last,
and maiden names, zip code, birthdate, and social security
u er.
METHODS
6. Participants
(a). Case-control study—Give the eligibility criteria, and
the sources and methods of case ascertainment and
control selection. Give the rationale for the choice of cases
and controls
METHODS
Example
Cuta eous ela o a ases diag osed i
a d
2000 were ascertained through the Iowa Cancer
Registry (...). Controls, also identified through the
Iowa Cancer Registry, were colorectal cancer
patients diagnosed during the same time. Colorectal
cancer controls were selected because they are
common and have a relatively long survival, and
because arsenic exposure has not been conclusively
linked to the incidence of colorectal a er.
METHODS
6. Participants
(a). Cross-sectional study—Give the eligibility criteria, and
the sources and methods of selection of participants
METHODS
Example
We retrospe ti el ide tified patie ts ith a pri ipal
diagnosis of myocardial infarction (code 410) according to the
International Classification of Diseases, 9th Revision, Clinical
Modification, from codes designating discharge diagnoses,
excluding the codes with a fifth digit of 2, which designates a
subsequent episode of care (. . .) A random sample of the
entire Medicare cohort with myocardial infarction from
February 1994 to July 1995 was selected (...) To be eligible,
patients had to present to the hospital after at least 30
minutes but less than 12 hours of chest pain and had to have
ST-segment elevation of at least 1 mm on two contiguous
leads on the initial ele tro ardiogra .
METHODS
6. Participants
(b). Cohort study: For matched studies, give
matching criteria and number of exposed and
unexposed.
METHODS
Example
For ea h patie t ho i itiall re ei ed a stati , e used
propensity-based matching to identify one control who did
not receive a statin according to the following protocol. First,
propensity scores were calculated for each patient in the
entire cohort on the basis of an extensive list of factors
potentially related to the use of statins or the risk of sepsis.
Second, each statin user was matched to a smaller pool of
non-statin-users by sex, age (plus or minus 1 year), and index
date (plus or minus 3 months). Third, we selected the control
with the closest propensity score (within 0.2 SD) to each
statin user in a 1:1 fashion and discarded the remaining
o trols.
METHODS
6. Participants
(b). Case-control study: For matched studies, give
matching criteria and the number of controls per
case.
METHODS
Example
We ai ed to sele t fi e o trols for e er ase fro
among individuals in the study population who had no
diagnosis of autism or other pervasive developmental
disorders (PDD) recorded in their general practice record
and who were alive and registered with a participating
practice on the date of the PDD diagnosis in the case.
Controls were individually matched to cases by year of
birth (up to 1 year older or younger), sex, and general
practice. For each of 300 cases, five controls could be
identified who met all the matching criteria. For the
re ai i g
, o e or ore o trols as e luded...
METHODS
7. Variables
Clearly define all outcomes, exposures, predictors,
potential confounders, and effect modifiers. Give
diagnostic criteria, if applicable
METHODS
Example
O l ajor o ge ital alfor atio s ere i luded i
the analyses. Minor anomalies were excluded according
to the exclusion list of European Registration of
Congenital Anomalies (EUROCAT). If a child had more
than one major congenital malformation of one organ
system, those malformations were treated as one
outcome in the analyses by organ system (...) In the
statistical analyses, factors considered potential
confounders were maternal age at delivery and number
of previous parities. Factors considered potential effect
modifiers were maternal age at reimbursement for
antiepileptic medication and maternal age at deli er .
METHODS
8. Data sources/measurement
For each variable of interest, give sources of data and
details of methods of assessment (measurement).
Describe comparability of assessment methods if there is
more than one group
METHODS
Example 1
Total affei e i take as al ulated pri aril usi g US
Department of Agriculture food composition sources. In these
calculations, it was assumed that the content of caffeine was 137
mg per cup of coffee, 47 mg per cup of tea, 46 mg per can or bottle
of cola beverage, and 7 mg per serving of chocolate candy. This
method of measuring (caffeine) intake was shown to be valid in
both the NHS I cohort and a similar cohort study of male health
professionals (...) Self-reported diagnosis of hypertension was
found to be reliable in the NHS I ohort.
Example 2
Sa ples pertai i g to at hed ases a d o trols ere al a s
analyzed together in the same batch and laboratory personnel
were unable to distinguish among cases and o trols.
METHODS
9. Bias
Describe any efforts to address potential
sources of bias
Example 1
I
ost ase-control studies of suicide, the control group
comprises living individuals but we decided to have a control
group of people who had died of other causes (. . .). With a
control group of deceased individuals, the sources of
information used to assess risk factors are informants who
have recently experienced the death of a family member or
close associate - and are therefore more comparable to the
sources of information in the suicide group than if living
controls were used.
METHODS
Example 2
Dete tio ias ould i flue e the asso iatio et ee
Type 2 diabetes mellitus (T2DM) and primary open-angle
glaucoma (POAG) if women with T2DM were under
closer ophthalmic surveillance than women without this
condition. We compared the mean number of eye
examinations reported by women with and without
diabetes. We also recalculated the relative risk for POAG
with additional control for covariates associated with
more careful ocular surveillance (a self-report of
cataract, macular degeneration, number of eye
examinations, and number of physical examinations .
METHODS
10. Study size
Explain how the study size was arrived at
Example 1
The u er of ases i the area duri g the stud period
determined the sample size.
Example 2
A sur e of post atal depressio i the regio had do u e ted a
prevalence of 19.8%. Assuming depression in mothers with normal
weight children to be 20% and an odds ratio of 3 for depression in
mothers with a malnourished child we needed 72 case-control sets
(one case to one control) with an 80% power and 5% sig ifi a e.
METHODS
11.Quantitative variables
Explain how quantitative variables were handled
in the analyses. If applicable, describe which
groupings were chosen, and why
Example
Patie ts ith a Glasgo Co a S ale less tha are
considered to be seriously injured. A GCS of 9 or more
indicates less serious brain injury. We examined the
association of GCS in these two categories with the
occurrence of death within 12 months from i jur .
METHODS
12. Statistical methods
(a) Describe all statistical methods, including
those used to control for confounding
Example
The adjusted relati e risk as al ulated usi g the
Mantel-Haenszel technique, when evaluating if
confounding by age or gender was present in the groups
compared. The 95% confidence interval (CI) was
computed around the adjusted relative risk, using the
variance according to Greenland and Robins and Robins
et al.
METHODS
12. Statistical methods
(b) Describe any methods used to examine subgroups and
interactions
METHODS
Example
Se differe es i sus epti ilit to the lifest le-related risk factors
studied were explored by testing for biological interaction according
to Rothman: a new composite variable with 4 categories (a-b-, a-b+,
a+b-, and a+b+) was redefined for sex and a dichotomous exposure of
interest where a and b denote absence of exposure. RR was
calculated for each category after adjustment for age. An interaction
effect is defined as departure from additivity of absolute effects,
and excess RR caused by interaction (RERI) was calculated:
RERI = RR(a+b+) – RR(a-b+) – RR(a+b-) - 1
Where RR(a+b+) denotes RR among those exposed to both factors
where RR(a-b-) is used as reference category (RR = 1.0). Ninety-five
percent CIs were calculated as proposed by Hosmer and Lemeshow.
RERI of 0 means no i tera tio .
METHODS
12. Statistical methods
(c) Explain how missing data were addressed
Example
Our issi g data a al sis pro edures used issi g at
random (MAR) assumptions. We used the MICE (multivariate
imputation by chained equations) method of multiple
multivariate imputation in STATA. We independently analysed
10 copies of the data, each with missing values suitably
imputed, in the multivariate logistic regression analyses. We
averaged estimates of the variables to give a single mean
esti ate a d adjusted sta dard errors a ordi g to ‘u i s
rules.
METHODS
12. Statistical methods
(d) Cohort study—If applicable, explain how loss to followup was addressed
Example
I treat e t programmes with active follow-up, those lost to
follow-up and those followed-up at 1 year had similar baseline
CD4 cell counts (median 115 cells per lL and 123 cells per lL),
whereas patients lost to follow-up in programmes with no
active follow-up procedures had considerably lower CD4 cell
counts than those followed-up (median 64 cells per lL and 123
cells per lL). (. . .) Treatment programmes with passive followup were excluded from subsequent a al ses.
METHODS
12. Statistical methods
(d) Case-control study—If applicable, explain how
matching of cases and controls was addressed
Example
We used M Ne ar s test, paired t test, and conditional
logistic regression analysis to compare dementia
patients with their matched controls for cardiovascular
risk factors, the occurrence of spontaneous cerebral
emboli, carotid disease, and venous to arterial
circulation shu t.
METHODS
12.Statistical methods
(d) Cross-sectional study: If applicable, describe
analytical methods taking account of sampling strategy.
Example
The sta dard errors SE ere al ulated usi g the Ta lor
expansion method to estimate the sampling errors of
estimators based on the complex sample design. (...) The
overall design effect for diastolic blood pressure was found to
be 1.9 for men and 1.8 for women and, for systolic blood
pressure, it as . for e a d . for o e
METHODS
12.Statistical methods
(e). Describe any sensitivity analyses.
Example
Be ause e had a relati el higher proportio of issi g dead
patie ts ith i suffi ie t data
/
⁄
. % as o pared to
li e patie ts
/
⁄ . % ... , it is possi le that this ight ha e
biased the results. We have, therefore, carried out a sensitivity
analysis. We have assumed that the proportion of women using
oral contraceptives in the study group applies to the whole (19.1%
for dead, and 11.4% for live patients), and then applied two
extreme scenarios: either all the exposed missing patients used
second generation pills or they all used third-generation pills.
RESULTS
13. Participants
(a) Report the numbers of individuals at each stage of the
study—e.g., numbers potentially eligible, examined for
eligibility, confirmed eligible, included in the study,
completing follow-up, and analysed
RESULTS
Example
Of the
freesta di g ars a d ta er s sa pled,
establishments were no longer in business and 9 were
located in restaurants, leaving 83 eligible businesses. In
22 cases, the owner could not be reached by telephone
despite 6 or more attempts. The owners of 36 bars
declined study participation. (...) The 25 participating
bars and taverns employed 124 bartenders, with 67
bartenders working at least 1 weekly daytime shift. Fiftyfour of the daytime bartenders (81%) completed
baseline interviews and spirometry; 53 of these subjects
(98%) completed follow-up.
RESULTS
13. Participants
(b) Give reasons for non-participation at each
stage
Example
The ai reaso s for o -participation were the
participant was too ill or had died before interview
(cases 30%, controls , 1%), nonresponse (cases 2%,
controls 21%), refusal (cases 10%, controls 29%), and
other reasons (refusal by consultant or general
practitioner, non-English speaking, mental impairment)
(cases 7%, controls 5% .
RESULTS
13. Participants
(c) Consider use of a flow diagram
. Flow diagram from Hay et al. [141].
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007) Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE): Explanation and Elaboration. PLOS Medicine 4(10): e297. https://doi.org/10.1371/journal.pmed.0040297
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0040297
RESULTS
14. Descriptive data
(a) Give characteristics of study participants (e.g.,
demographic, clinical, social) and information on
exposures and potential confounders
RESULTS
14. Descriptive data
(b) Indicate the number of participants with missing data
for each variable of interest
RESULTS
14. Descriptive data
(c) Cohort study—Summarise follow-up time
(e.g., average and total amount)
Example
Duri g the
perso -years of follow-up (median
5.4, maximum 8.3 years), 265 subjects were
diagnosed as having dementia, including 202 with
Alzhei er s disease.
RESULTS
15. Outcome data
Cohort study—Report numbers of outcome events or
summary measures over time
RESULTS
15. Outcome data
Case-control study—Report numbers in each exposure
category, or summary measures of exposure
RESULTS
15. Outcome data
Cross-sectional study—Report numbers of outcome
events or summary measures
RESULTS
16. Main results
(a) Give unadjusted estimates and, if applicable,
confounder-adjusted estimates and their precision (e.g.,
95% confidence interval).
Make clear which confounders were adjusted for and why
they were included
Example 1
We i itiall o sidered the follo i g aria les as pote tial
confounders by Mantel-Haenszel stratified analysis: (. . .) The
variables we included in the final logistic regression models
were those (. . .) that produced a 10% change in the odds
ratio after the Mantel-Haenszel adjust e t.
RESULTS
16. Main results
(b) Report category boundaries when continuous variables
were categorized
RESULTS
16. Main results
(c) If relevant, consider translating estimates of
relative risk into absolute risk for a meaningful
time period
Example
ears use of H‘T [hor o e repla e e t therap ] is
estimated to result in five (95% CI 3–7) additional breast
cancers per 1000 users of oestrogen-only preparations
and 19 (15–23) additional cancers per 1000 users of
oestrogen-progestagen o i atio s.
RESULTS
17. Other analyses
Report other analyses done—e.g., analyses of subgroups
and interactions, and sensitivity analyses
DISCUSSION
18. Key results
Summarise key results with reference to study objectives
Example
We h pothesized that eth i i orit status ould e asso iated
with higher levels of cardiovascular disease (CVD) risk factors, but
that the associations would be explained substantially by
socioeconomic status (SES). Our hypothesis was not confirmed.
After adjustment for age and SES, highly significant differences in
body mass index, blood pressure, diabetes, and physical inactivity
remained between white women and both black and Mexican
American women. In addition, we found large differences in CVD
risk factors by SES, a finding that illustrates the high-risk status of
both ethnic minority women as well as white women with low
SES.
DISCUSSION
19. Limitations
Discuss limitations of the study, taking into account sources of
potential bias or imprecision. Discuss both direction and magnitude of
any potential bias
Example
Si e the pre ale e of ou seli g i reases ith i reasi g le els of
obesity, our estimates may overestimate the true prevalence. Telephone
surveys also may over- estimate the true prevalence of counseling.
Although persons without telephones have similar levels of overweight as
persons with telephones, persons without telephones tend to be less
educated, a factor associated with lower levels of counseling in our study.
Also, of concern is the potential bias caused by those who refused to
participate as well as those who refused to respond to questions about
weight. Further- more, because data were collected cross-sectionally, we
a ot i fer that ou seli g pre eded a patie t s atte pt to lose eight.
DISCUSSION
20. Interpretation
Give a cautious overall interpretation of results
considering objectives, limitations, multiplicity of
analyses, results from similar studies, and other
relevant evidence
Example
A e pla atio for a asso iatio et ee death fro
o ardial
infarction and use of second generation oral contraceptives must be
conjectural. There is no published evidence to suggest a direct biologic
mechanism, and there are no other epidemiologic studies with relevant
results. (. . .) The increase in absolute risk is very small and probably
applies predominantly to smokers. Due to the lack of corroborative
evidence, and because the analysis is based on relatively small numbers,
more evidence on the subject is needed. We would not recommend any
change in prescribing practice on the strength of these results.
DISCUSSION
21. Generalisability
Discuss the generalisability (external validity) of the study
results
Example
Ho appli a le are our esti ates to other HIV-1-infected patients? This
is an important question because the accuracy of prognostic models
tends to be lower when applied to data other than those used to develop
them. We addressed this issue by penalising model complexity, and by
choosing models that generalised best to cohorts omitted from the
estimation procedure. Our database included patients from many
countries from Europe and North America, who were treated in different
settings. The range of patients was broad: men and women, from
teenagers to elderly people were included, and the major exposure
categories were well represented. The severity of immunodeficiency at
baseline ranged from not measureable to very severe, and viral load from
undetectable to extremely high.
OTHER INFORMATION
22. Funding
Give the source of funding and the role of the funders for
the present study and, if applicable, for the original study
on which the present article is based
Observational studies in Epidemiology
(STROBE)
Table 1.
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007) Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE): Explanation and Elaboration. PLOS Medicine 4(10): e297. https://doi.org/10.1371/journal.pmed.0040297
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0040297
TITLE and ABSTRACT
1.
(a I di ate the stud s desig ith a o
used term in the title or the abstract
Example
o l
Leukaemia incidence among workers in the shoe
and boot manufacturing industry: a case-control
stud
TITLE and ABSTRACT
1.
(b) Provide in the abstract an informative and
balanced summary of what was done and what
was found
TITLE and ABSTRACT
Example
Background: The expected survival of HIV-infected
patients is of major public health interest.
Objective: To estimate survival time and age-specific
mortality rates of an HIV-infected population
compared with that of the general population.
Design: Population-based cohort study.
Setting: All HIV-infected persons receiving care in
Denmark from 1995 to 2005.
TITLE and ABSTRACT
Example
Patients: Each member of the nationwide Danish HIV
Cohort Study was matched with as many as 99 persons
from the general population according to sex, date of
birth, and municipality of residence.
Measurements: The authors computed Kaplan–Meier
life tables with age as the time scale to estimate survival
from age 25 years. Patients with HIV infection and
corresponding persons from the general population
ere o ser ed fro the date of the patie t s HIV
diagnosis until death, emigration, or 1 May 2005.
TITLE and ABSTRACT
Example
Results: 3990 HIV-infected patients and 379 872 persons from the
general population were included in the study, yielding 22 744
(median, 5.8 y/person) and 2 689 287 (median, 8.4 years/person)
person-years of observation. Three percent of participants were
lost to follow-up. From age 25 years, the median survival was 19.9
years (95% CI, 18.5 to 21.3) among patients with HIV infection and
51.1 years (CI, 50.9 to 51.5) among the general population. For HIVinfected patients, survival increased to 32.5 years (CI, 29.4 to 34.7)
during the 2000 to 2005 period. In the subgroup that excluded
persons with known hepatitis C coinfection (16%), median survival
was 38.9 years (CI, 35.4 to 40.1) during this same period. The
relative mortality rates for patients with HIV infection compared
with those for the general population decreased with increasing
age, whereas the excess mortality rate increased with increasing
age.
TITLE and ABSTRACT
Example
Limitations: The observed mortality rates are
assumed to apply beyond the current maximum
observation time of 10 years.
Conclusions: The estimated median survival is more
than 35 years for a young person diagnosed with HIV
infection in the late highly active antiretroviral
therapy era. However, an ongoing effort is still
needed to further reduce mortality rates for these
persons compared with the general population.
INTRODUCTION
2. Background/rationale
Explain the scientific background and rationale for the
investigation being reported
INTRODUCTION
Example
Co er s a out the risi g pre ale e of o esit i hildre a d
adolescents have focused on the well documented associations between
childhood obesity and in- creased cardiovascular risk and mortality in
adulthood. Childhood obesity has considerable social and psychological
consequences within childhood and adolescence, yet little is known about
social, socioeconomic, and psychological con- sequences in adult life. A
recent systematic review found no longitudinal studies on the outcomes
of childhood obesity other than physical health outcomes and only two
longitudinal studies of the socioeconomic effects of obesity in
adolescence. Gortmaker et al. found that US women who had been obese
in late adolescence in 1981 were less likely to be married and had lower
incomes seven years later than women who had not been overweight,
while men who had been overweight were less likely to be married.
Sargent et al. found that UK women, but not men, who had been obese at
16 years in 1974 earned 7.4% less than their non-obese peers at age 23. (.
. .) We used longitudinal data from the 1970 British birth cohort to
examine the adult socioeconomic, educational, social, and psychological
out o es of hildhood o esit
INTRODUCTION
3. Objectives
State specific objectives, including any prespecified
hypotheses
INTRODUCTION
Example
Our pri ar o je ti es ere to deter i e the
prevalence of domestic violence among female
patients presenting to four community-based,
primary care, adult medicine practices that serve
patients of diverse socio- economic background and
2) identify demographic and clinical differences
between currently abused patients and patients not
currently being abused.
METHODS
4. Study design
Present key elements of study design early in the paper
METHODS
Example
We used a ase-crossover design, a variation of a case- control
desig that is appropriate he a rief e posure dri er s pho e
use) causes a transient rise in the risk of a rare outcome (a crash).
We o pared a dri er s use of a o ile pho e at the esti ated
ti e of a rash ith the sa e dri er s use duri g a other suita le
time period. Because drivers are their own controls, the design
controls for characteristics of the driver that may affect the risk of a
crash but do not change over a short period of time. As it is
important that risks during control periods and crash trips are
similar, we compared phone activity during the hazard interval
(time immediately before the crash) with phone activity during
control intervals (equivalent times during which participants were
driving but did not crash) in the previous eek.
METHODS
5. Setting
Describe the setting, locations, and relevant dates,
including periods of recruitment, exposure, follow-up, and
data collection
METHODS
Example
The Pasitos Cohort Study recruited pregnant women
from Women, Infant and Child clinics in Socorro and San
Elizario, El Paso County, Texas and maternal-child clinics
of the Mexican Social Security Institute in Ciudad Juarez,
Mexico from April 1998 to October 2000. At baseline,
prior to the birth of the enrolled cohort children, staff
interviewed mothers regarding the household
environment. In this ongoing cohort study, we target
follow-up exams at 6-month intervals beginning at age 6
o ths.
METHODS
6. Participants
(a). Cohort study—Give the eligibility criteria, and the
sources and methods of selection of participants. Describe
methods of follow-up
METHODS
Example
Parti ipa ts i the Io a Wo e s Health Stud ere a
random sample of all women ages 55 to 69 years derived
fro the state of Io a auto o ile dri er s li e se list i
,
which represented approximately 94% of Iowa women in that
age group. (. . .) Follow-up questionnaires were mailed in
October 1987 and August 1989 to assess vital status and
address changes. (. . .) Incident cancers, except for nonmelanoma skin cancers, were ascertained by the State Health
‘egistr of Io a . . . . The Io a Wo e s Health Stud ohort
was matched to the registry with combinations of first, last,
and maiden names, zip code, birthdate, and social security
u er.
METHODS
6. Participants
(a). Case-control study—Give the eligibility criteria, and
the sources and methods of case ascertainment and
control selection. Give the rationale for the choice of cases
and controls
METHODS
Example
Cuta eous ela o a ases diag osed i
a d
2000 were ascertained through the Iowa Cancer
Registry (...). Controls, also identified through the
Iowa Cancer Registry, were colorectal cancer
patients diagnosed during the same time. Colorectal
cancer controls were selected because they are
common and have a relatively long survival, and
because arsenic exposure has not been conclusively
linked to the incidence of colorectal a er.
METHODS
6. Participants
(a). Cross-sectional study—Give the eligibility criteria, and
the sources and methods of selection of participants
METHODS
Example
We retrospe ti el ide tified patie ts ith a pri ipal
diagnosis of myocardial infarction (code 410) according to the
International Classification of Diseases, 9th Revision, Clinical
Modification, from codes designating discharge diagnoses,
excluding the codes with a fifth digit of 2, which designates a
subsequent episode of care (. . .) A random sample of the
entire Medicare cohort with myocardial infarction from
February 1994 to July 1995 was selected (...) To be eligible,
patients had to present to the hospital after at least 30
minutes but less than 12 hours of chest pain and had to have
ST-segment elevation of at least 1 mm on two contiguous
leads on the initial ele tro ardiogra .
METHODS
6. Participants
(b). Cohort study: For matched studies, give
matching criteria and number of exposed and
unexposed.
METHODS
Example
For ea h patie t ho i itiall re ei ed a stati , e used
propensity-based matching to identify one control who did
not receive a statin according to the following protocol. First,
propensity scores were calculated for each patient in the
entire cohort on the basis of an extensive list of factors
potentially related to the use of statins or the risk of sepsis.
Second, each statin user was matched to a smaller pool of
non-statin-users by sex, age (plus or minus 1 year), and index
date (plus or minus 3 months). Third, we selected the control
with the closest propensity score (within 0.2 SD) to each
statin user in a 1:1 fashion and discarded the remaining
o trols.
METHODS
6. Participants
(b). Case-control study: For matched studies, give
matching criteria and the number of controls per
case.
METHODS
Example
We ai ed to sele t fi e o trols for e er ase fro
among individuals in the study population who had no
diagnosis of autism or other pervasive developmental
disorders (PDD) recorded in their general practice record
and who were alive and registered with a participating
practice on the date of the PDD diagnosis in the case.
Controls were individually matched to cases by year of
birth (up to 1 year older or younger), sex, and general
practice. For each of 300 cases, five controls could be
identified who met all the matching criteria. For the
re ai i g
, o e or ore o trols as e luded...
METHODS
7. Variables
Clearly define all outcomes, exposures, predictors,
potential confounders, and effect modifiers. Give
diagnostic criteria, if applicable
METHODS
Example
O l ajor o ge ital alfor atio s ere i luded i
the analyses. Minor anomalies were excluded according
to the exclusion list of European Registration of
Congenital Anomalies (EUROCAT). If a child had more
than one major congenital malformation of one organ
system, those malformations were treated as one
outcome in the analyses by organ system (...) In the
statistical analyses, factors considered potential
confounders were maternal age at delivery and number
of previous parities. Factors considered potential effect
modifiers were maternal age at reimbursement for
antiepileptic medication and maternal age at deli er .
METHODS
8. Data sources/measurement
For each variable of interest, give sources of data and
details of methods of assessment (measurement).
Describe comparability of assessment methods if there is
more than one group
METHODS
Example 1
Total affei e i take as al ulated pri aril usi g US
Department of Agriculture food composition sources. In these
calculations, it was assumed that the content of caffeine was 137
mg per cup of coffee, 47 mg per cup of tea, 46 mg per can or bottle
of cola beverage, and 7 mg per serving of chocolate candy. This
method of measuring (caffeine) intake was shown to be valid in
both the NHS I cohort and a similar cohort study of male health
professionals (...) Self-reported diagnosis of hypertension was
found to be reliable in the NHS I ohort.
Example 2
Sa ples pertai i g to at hed ases a d o trols ere al a s
analyzed together in the same batch and laboratory personnel
were unable to distinguish among cases and o trols.
METHODS
9. Bias
Describe any efforts to address potential
sources of bias
Example 1
I
ost ase-control studies of suicide, the control group
comprises living individuals but we decided to have a control
group of people who had died of other causes (. . .). With a
control group of deceased individuals, the sources of
information used to assess risk factors are informants who
have recently experienced the death of a family member or
close associate - and are therefore more comparable to the
sources of information in the suicide group than if living
controls were used.
METHODS
Example 2
Dete tio ias ould i flue e the asso iatio et ee
Type 2 diabetes mellitus (T2DM) and primary open-angle
glaucoma (POAG) if women with T2DM were under
closer ophthalmic surveillance than women without this
condition. We compared the mean number of eye
examinations reported by women with and without
diabetes. We also recalculated the relative risk for POAG
with additional control for covariates associated with
more careful ocular surveillance (a self-report of
cataract, macular degeneration, number of eye
examinations, and number of physical examinations .
METHODS
10. Study size
Explain how the study size was arrived at
Example 1
The u er of ases i the area duri g the stud period
determined the sample size.
Example 2
A sur e of post atal depressio i the regio had do u e ted a
prevalence of 19.8%. Assuming depression in mothers with normal
weight children to be 20% and an odds ratio of 3 for depression in
mothers with a malnourished child we needed 72 case-control sets
(one case to one control) with an 80% power and 5% sig ifi a e.
METHODS
11.Quantitative variables
Explain how quantitative variables were handled
in the analyses. If applicable, describe which
groupings were chosen, and why
Example
Patie ts ith a Glasgo Co a S ale less tha are
considered to be seriously injured. A GCS of 9 or more
indicates less serious brain injury. We examined the
association of GCS in these two categories with the
occurrence of death within 12 months from i jur .
METHODS
12. Statistical methods
(a) Describe all statistical methods, including
those used to control for confounding
Example
The adjusted relati e risk as al ulated usi g the
Mantel-Haenszel technique, when evaluating if
confounding by age or gender was present in the groups
compared. The 95% confidence interval (CI) was
computed around the adjusted relative risk, using the
variance according to Greenland and Robins and Robins
et al.
METHODS
12. Statistical methods
(b) Describe any methods used to examine subgroups and
interactions
METHODS
Example
Se differe es i sus epti ilit to the lifest le-related risk factors
studied were explored by testing for biological interaction according
to Rothman: a new composite variable with 4 categories (a-b-, a-b+,
a+b-, and a+b+) was redefined for sex and a dichotomous exposure of
interest where a and b denote absence of exposure. RR was
calculated for each category after adjustment for age. An interaction
effect is defined as departure from additivity of absolute effects,
and excess RR caused by interaction (RERI) was calculated:
RERI = RR(a+b+) – RR(a-b+) – RR(a+b-) - 1
Where RR(a+b+) denotes RR among those exposed to both factors
where RR(a-b-) is used as reference category (RR = 1.0). Ninety-five
percent CIs were calculated as proposed by Hosmer and Lemeshow.
RERI of 0 means no i tera tio .
METHODS
12. Statistical methods
(c) Explain how missing data were addressed
Example
Our issi g data a al sis pro edures used issi g at
random (MAR) assumptions. We used the MICE (multivariate
imputation by chained equations) method of multiple
multivariate imputation in STATA. We independently analysed
10 copies of the data, each with missing values suitably
imputed, in the multivariate logistic regression analyses. We
averaged estimates of the variables to give a single mean
esti ate a d adjusted sta dard errors a ordi g to ‘u i s
rules.
METHODS
12. Statistical methods
(d) Cohort study—If applicable, explain how loss to followup was addressed
Example
I treat e t programmes with active follow-up, those lost to
follow-up and those followed-up at 1 year had similar baseline
CD4 cell counts (median 115 cells per lL and 123 cells per lL),
whereas patients lost to follow-up in programmes with no
active follow-up procedures had considerably lower CD4 cell
counts than those followed-up (median 64 cells per lL and 123
cells per lL). (. . .) Treatment programmes with passive followup were excluded from subsequent a al ses.
METHODS
12. Statistical methods
(d) Case-control study—If applicable, explain how
matching of cases and controls was addressed
Example
We used M Ne ar s test, paired t test, and conditional
logistic regression analysis to compare dementia
patients with their matched controls for cardiovascular
risk factors, the occurrence of spontaneous cerebral
emboli, carotid disease, and venous to arterial
circulation shu t.
METHODS
12.Statistical methods
(d) Cross-sectional study: If applicable, describe
analytical methods taking account of sampling strategy.
Example
The sta dard errors SE ere al ulated usi g the Ta lor
expansion method to estimate the sampling errors of
estimators based on the complex sample design. (...) The
overall design effect for diastolic blood pressure was found to
be 1.9 for men and 1.8 for women and, for systolic blood
pressure, it as . for e a d . for o e
METHODS
12.Statistical methods
(e). Describe any sensitivity analyses.
Example
Be ause e had a relati el higher proportio of issi g dead
patie ts ith i suffi ie t data
/
⁄
. % as o pared to
li e patie ts
/
⁄ . % ... , it is possi le that this ight ha e
biased the results. We have, therefore, carried out a sensitivity
analysis. We have assumed that the proportion of women using
oral contraceptives in the study group applies to the whole (19.1%
for dead, and 11.4% for live patients), and then applied two
extreme scenarios: either all the exposed missing patients used
second generation pills or they all used third-generation pills.
RESULTS
13. Participants
(a) Report the numbers of individuals at each stage of the
study—e.g., numbers potentially eligible, examined for
eligibility, confirmed eligible, included in the study,
completing follow-up, and analysed
RESULTS
Example
Of the
freesta di g ars a d ta er s sa pled,
establishments were no longer in business and 9 were
located in restaurants, leaving 83 eligible businesses. In
22 cases, the owner could not be reached by telephone
despite 6 or more attempts. The owners of 36 bars
declined study participation. (...) The 25 participating
bars and taverns employed 124 bartenders, with 67
bartenders working at least 1 weekly daytime shift. Fiftyfour of the daytime bartenders (81%) completed
baseline interviews and spirometry; 53 of these subjects
(98%) completed follow-up.
RESULTS
13. Participants
(b) Give reasons for non-participation at each
stage
Example
The ai reaso s for o -participation were the
participant was too ill or had died before interview
(cases 30%, controls , 1%), nonresponse (cases 2%,
controls 21%), refusal (cases 10%, controls 29%), and
other reasons (refusal by consultant or general
practitioner, non-English speaking, mental impairment)
(cases 7%, controls 5% .
RESULTS
13. Participants
(c) Consider use of a flow diagram
. Flow diagram from Hay et al. [141].
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007) Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE): Explanation and Elaboration. PLOS Medicine 4(10): e297. https://doi.org/10.1371/journal.pmed.0040297
http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0040297
RESULTS
14. Descriptive data
(a) Give characteristics of study participants (e.g.,
demographic, clinical, social) and information on
exposures and potential confounders
RESULTS
14. Descriptive data
(b) Indicate the number of participants with missing data
for each variable of interest
RESULTS
14. Descriptive data
(c) Cohort study—Summarise follow-up time
(e.g., average and total amount)
Example
Duri g the
perso -years of follow-up (median
5.4, maximum 8.3 years), 265 subjects were
diagnosed as having dementia, including 202 with
Alzhei er s disease.
RESULTS
15. Outcome data
Cohort study—Report numbers of outcome events or
summary measures over time
RESULTS
15. Outcome data
Case-control study—Report numbers in each exposure
category, or summary measures of exposure
RESULTS
15. Outcome data
Cross-sectional study—Report numbers of outcome
events or summary measures
RESULTS
16. Main results
(a) Give unadjusted estimates and, if applicable,
confounder-adjusted estimates and their precision (e.g.,
95% confidence interval).
Make clear which confounders were adjusted for and why
they were included
Example 1
We i itiall o sidered the follo i g aria les as pote tial
confounders by Mantel-Haenszel stratified analysis: (. . .) The
variables we included in the final logistic regression models
were those (. . .) that produced a 10% change in the odds
ratio after the Mantel-Haenszel adjust e t.
RESULTS
16. Main results
(b) Report category boundaries when continuous variables
were categorized
RESULTS
16. Main results
(c) If relevant, consider translating estimates of
relative risk into absolute risk for a meaningful
time period
Example
ears use of H‘T [hor o e repla e e t therap ] is
estimated to result in five (95% CI 3–7) additional breast
cancers per 1000 users of oestrogen-only preparations
and 19 (15–23) additional cancers per 1000 users of
oestrogen-progestagen o i atio s.
RESULTS
17. Other analyses
Report other analyses done—e.g., analyses of subgroups
and interactions, and sensitivity analyses
DISCUSSION
18. Key results
Summarise key results with reference to study objectives
Example
We h pothesized that eth i i orit status ould e asso iated
with higher levels of cardiovascular disease (CVD) risk factors, but
that the associations would be explained substantially by
socioeconomic status (SES). Our hypothesis was not confirmed.
After adjustment for age and SES, highly significant differences in
body mass index, blood pressure, diabetes, and physical inactivity
remained between white women and both black and Mexican
American women. In addition, we found large differences in CVD
risk factors by SES, a finding that illustrates the high-risk status of
both ethnic minority women as well as white women with low
SES.
DISCUSSION
19. Limitations
Discuss limitations of the study, taking into account sources of
potential bias or imprecision. Discuss both direction and magnitude of
any potential bias
Example
Si e the pre ale e of ou seli g i reases ith i reasi g le els of
obesity, our estimates may overestimate the true prevalence. Telephone
surveys also may over- estimate the true prevalence of counseling.
Although persons without telephones have similar levels of overweight as
persons with telephones, persons without telephones tend to be less
educated, a factor associated with lower levels of counseling in our study.
Also, of concern is the potential bias caused by those who refused to
participate as well as those who refused to respond to questions about
weight. Further- more, because data were collected cross-sectionally, we
a ot i fer that ou seli g pre eded a patie t s atte pt to lose eight.
DISCUSSION
20. Interpretation
Give a cautious overall interpretation of results
considering objectives, limitations, multiplicity of
analyses, results from similar studies, and other
relevant evidence
Example
A e pla atio for a asso iatio et ee death fro
o ardial
infarction and use of second generation oral contraceptives must be
conjectural. There is no published evidence to suggest a direct biologic
mechanism, and there are no other epidemiologic studies with relevant
results. (. . .) The increase in absolute risk is very small and probably
applies predominantly to smokers. Due to the lack of corroborative
evidence, and because the analysis is based on relatively small numbers,
more evidence on the subject is needed. We would not recommend any
change in prescribing practice on the strength of these results.
DISCUSSION
21. Generalisability
Discuss the generalisability (external validity) of the study
results
Example
Ho appli a le are our esti ates to other HIV-1-infected patients? This
is an important question because the accuracy of prognostic models
tends to be lower when applied to data other than those used to develop
them. We addressed this issue by penalising model complexity, and by
choosing models that generalised best to cohorts omitted from the
estimation procedure. Our database included patients from many
countries from Europe and North America, who were treated in different
settings. The range of patients was broad: men and women, from
teenagers to elderly people were included, and the major exposure
categories were well represented. The severity of immunodeficiency at
baseline ranged from not measureable to very severe, and viral load from
undetectable to extremely high.
OTHER INFORMATION
22. Funding
Give the source of funding and the role of the funders for
the present study and, if applicable, for the original study
on which the present article is based